Heart rate is dominated by the tonic activity of the cardioinhibitory parasympathetic nervous system. Parasympathetic activity to the heart also influences coronary blood flow and the inotropic state of cardiac muscle. An impairment in parasympathetic innervation of the heart has been implicated in diseases such as hypertension, ischemic heart disease and sudden cardiac death. Surprisingly, however, little is known concerning the origin or control of parasympathetic cardiac activity within the central nervous system. In this study I will test a number of important hypotheses concerning the origin, and synaptic modulation of preganglionic parasympathetic cardiac activity. This project combines a novel technique that I have developed to identify and isolate preganglionic parasympathetic cardiac neurons with patch clamp methodology. The synthesis of these techniques will enable me to characterize the electrophysiological properties of identified cardiovascular neurons at a cellular level. There are 4 major and distinct aims. I will: 1) Test the hypothesis that preganglionic parasympathetic cardiac neurons, isolated from their surrounding tissue in the medulla, fire spontaneously and repetitively; 2) Characterize, using patch clamp techniques, the voltage-gated ionic currents in these cardiac neurons; 3) Test the hypothesis that acetylcholine and opioid neurotransmitters influence the activity of preganglionic parasympathetic cardiac neurons. I will also identify other neurotransmitters that are most likely to influence the activity of preganglionic cardiac neurons; and 4) Characterize the ionic currents that are evoked by these neurotransmitters, and the effects of these neurotransmitters on the voltage-gated currents. The results from this project will provide new and unique information, at the cellular level, concerning the origin, and synaptic regulation of parasympathetic activity that innervates the heart.GRANT=R15HL50123 Fitness enthusiasts, laborers, and athletes need activity guidelines during an upper respiratory illness (URI). Further, fitness levels may be demonstrated to impact on the severity and duration of an URI and the musculoskeletal and cardiorespiratory responses to an URI. Results of this study will be used to make recommendations regarding physical activity levels during an episode of URI. The objectives of the study are as follows: l) to determine the impact of an URI on exercise functional capacity; 2) to determine whether a person's fitness level is related to exercise functional capacity during an URI; 3) to determine the impact of exercise on both the severity and duration of an URI; 4) to determine whether a person's fitness level is related to the severity and duration of an URI. Subjects will be exercise tested and assigned to a fit or unfit group. Within each of these groups, subjects will be randomly assigned to either a control or experimental group. Subjects will be inoculated with rhinovirus 16 (RV16). In the first phase (year one) of the study, the subsequent impact of moderate exercise training on the severity and duration of an URI will be determined. In the second phase (year two) of the study, the impact of an URI during peak illness (days 2 and 3) on the exercise functional capacity of infected subjects will be determined. Differences in group data will be analyzed.